Sixty years after Cleveland Clinic researchers first isolated the role of angiotensin II in controlling blood pressure, a new international study led by Cleveland Clinic researchers shows that the compound can safely improve blood pressure among critically ill patients who are experiencing life-threatening hypotension, or low blood pressure.

The research - led by Ashish Khanna, M.D., an intensivist and anesthesiologist in Cleveland Clinic's Center for Critical Care - will be published online by the New England Journal of Medicine, in conjunction with the American Thoracic Society's special session on clinical research.

"Vasodilatory shock - in which a patient's blood pressure drops and blood vessels dilate - is a serious concern for ICU patients. When the condition is not responsive to high-dose vasopressors like norepinephrine and vasopressin, it is associated with high mortality, with more than half of these patients dying within 30 days," Dr. Khanna said. "We found that angiotensin II is an effective intervention for these patients, significantly increasing blood pressure in this life-threatening situation. The drug was safe and well-tolerated and also showed a trend to decreased mortality, though this did not achieve clinical significance."

The study enrolled 321 patients - 163 treated with angiotensin II and 158 with placebo - who were experiencing vasodilatory shock and had received high doses of conventional vasopressors.

The trial was conducted in 75 intensive care units across nine countries in North America, Australia and Europe.

Angiotensin II was first isolated at Cleveland Clinic in the 1950s by Irvine Page, M.D., who discovered that the substance in blood causes blood vessels to constrict and blood pressure to rise. Along with co-researcher F. Merlin Bumpus, Ph.D., Page synthesized the peptide in 1957, helping to shape medicine's understanding of blood pressure and heart disease. For the first time, high blood pressure was viewed as a condition that could be treated, by blocking the body's production on angiotensin II.

In this new research, the goal was to raise blood pressure in critically ill patients in vasodilatory shock by providing exogenous Angiotensin II. It is the first and largest phase III randomized controlled trial of stable, synthetic human angiotensin II.

It was conducted under a special protocol assessment with the US Food and Drug Administration, which considers an uncompleted Phase III trial's design, clinical endpoints, and statistical analyses acceptable for FDA approval.

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The study was funded by La Jolla Pharmaceutical Inc. (ClinicalTrials.gov number NCT02338843) and completed with internal support from the Department of Outcomes Research, and the Anesthesiology Institute at the Cleveland Clinic.

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Among Cleveland Clinic's 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic's health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations - including 18 full-service family health centers and three health and wellness centers - and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic's health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org.

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